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Saturation of, and competition for entry into, the apical secretory pathway

2000; National Academy of Sciences; Volume: 97; Issue: 7 Linguagem: Inglês

10.1073/pnas.97.7.3248

1091-6490

Alan D. Marmorstein, Karl G. Csaky, Judit Baffi, Linda Lam, Firas Rahaal, Enrique Rodriguez‐Boulan,

Galectins and Cancer Biology

To investigate mechanisms of apical sorting in the secretory pathway of epithelial cells, we expressed varying amounts of the 165 amino acid isoform of vascular endothelial growth factor (VEGF 165 ) and transforming growth factor β1 (TGF-β1) via replication defective adenoviruses. Apical sorting of both proteins was efficient at low expression levels but saturated or was reversed at high expression levels. High expression levels of TGF-β1 were effective at competing VEGF 165 out of the apical pathway; however, VEGF 165 did not compete out TGF-β1. Tunicamycin inhibition experiments showed that the apical polarity of VEGF 165 was independent of N -glycosylation. We conclude that the apical sorting of these two molecules is a saturable, signal-mediated process, involving competition for apical sorting receptors. The sorting of the two proteins does not appear to involve N -glycans as sorting signals, or lectin sorters. The observations are particularly relevant to gene therapy because they demonstrate that overexpression of a transgene can result in undesirable missorting of the encoded protein.